%0 Journal Article
%T Reduced phosphodiesterase
%A Gang Wang
%A Gaowen Li
%A Haiyang Yu
%A Han-Ting Zhang
%A James M OĦŻDonnell
%A Ling Chen
%A Na Liu
%A Qiang Wu
%A Suying Cui
%A Ying Xu
%J Journal of Psychopharmacology
%@ 1461-7285
%D 2019
%R 10.1177/0269881119832753
%X Phosphodiesterase-2 (PDE2) is a cyclic nucleotide phosphodiesterase and is highly expressed in the amygdala, which suggests its important role in anxiety-like behavior. The present study examined whether reduced PDE2A expression in the central nucleus of the amygdala (CeA) produces anxiolytic-like effects in mice. PDE2A knockdown in amygdaloid (AR5) cells or the CeA was established using a lentiviral vector-based siRNA system. The anxiety-like behaviors were detected by the elevated plus maze (EPM) and hole-board tests in mice. The related proteins involved in cAMP/cGMP-dependent signaling, such as specific marker VASPser239, CREBser133 and BDNF were detected by immunoblot analysis. PDE2A inhibition in AR-5 cells resulted in increases in cAMP/cGMP-related pVASPser239 and pCREBser133. Behavioral tests showed that PDE2A knockdown in the CeA induced anxiolytic-like effects as evidenced by the increases in percentages of open-arm entries and time spent in the open arms in the EPM test, and the increases in head dips and time spent in head dipping in the hole-board test. However, these anxiolytic-like effects were antagonized by pre-treatment of soluble guanylyl cyclase inhibitor ODQ or adenylate cyclase inhibitor SQ. Furthermore, PDE2A knockdown significantly increased pVASPSer239, pCREBSer133 and decreased BDNF expression in the amygdala. Pre-intra-CeA of ODQ or SQ reversed or partially prevented the e£żects of PDE2A knockdown on these proteins. The results suggest that PDE2A plays a crucial role in the regulation of anxiety by the cGMP/cAMP-dependent pVASP-pCREB-BDNF signaling pathway
%K PDE2
%K anxiety
%K cGMP/cAMP
%K pVASP
%K pCREB
%K central nucleus of the amygdala (CeA)
%U https://journals.sagepub.com/doi/full/10.1177/0269881119832753